N-substituted-p-(2-chloroethyl)-phosphonamidates

ABSTRACT

Plant growth regulating compounds are N-substituted-P-(2chloroethyl)-phosphonamidic esters of the formula: WHEREIN R1 is halophenyl and R2 is alkyl or haloalkyl. They are prepared by the reaction of 2-chloroethylphosphonohalidic esters with the appropriate haloaniline.

United States Patent Randall et al. July 25, 1972 54]N-SUBSTITUTED-H2-CHLOROETHYL)- 2,765,276 l0/l956 Van Winkle et al...260/959 x PHOSPHONAMIDATES Primary ExaminerJoseph Rebold [72]Inventors: David I. Randall; Robert W. Wynn, both Assismm ExaminerRichal-d Raymond of Easton Atrorne vSamson B. Leavitt and Walter C.Kehon 73 Assi nee: GAF Cor oration New York, NY. l 1 g p 57 ABSTRACT 22Filed: Dec. 2, 1969 Plant growth regulating compounds areN-substltuted-P-(Z- PP 831,579 chloroethyl)-phosphonamidic esters of theformula:

52 us. 0 ..260/959 [51] Int. Cl ClCHgCIIzlNH-R [58] Field of Search..260/959 R2 [56] References cued wherein R is halophenyl and R is alkylor haloalkyl. They are UNITED STATES PATENTS prepared by the reaction of2-chloroethylphosphonohalidic esters with the appropriate haloaniline.3,253,062 5/1966 Reetz et al. ......260/959 X 3,531,550 9/1970 Herber etal ..260/959 6 Claims, No Drawings N-SUBSTITUTED-P-(Z-CI-ILOROE'IHYD-PHOSPHONAMIDATES BACKGROUND OF THE INVENTION 1. Field of the InventionThis invention relates to N-mono-substituted-P-( 2- chloroethyl)phosphonamidate compounds useful as plant growth regulators andprocesses for their preparation.

2. Background of the Prior Art The art is aware that certainphosphoruscontaining compounds are useful as plant growth regulators.One of the most important phosphorus compounds of this class is 2-chloroethyl-phosphonic acid which has found importance as a plant growthregulator, particularly in the treatment of pineapples and soy beans tocontrol their rate of growth. The present invention provides a new classof phosphorus-containing compounds useful as plant growth regulators notknown heretofore, which compounds have utility in this area equivalentto 2-chloroethyl phosphonic acid. One of the primary characteristics ofproducts of this type is the presence of the 2-chloroethyl group as thecompounds are absorbed by the plant and release ethylene, a known plantregulator, in a form in which it can be used by the plant.

The art teaches various nitrogen-substituted phosphonamidates but noneare suggested as having plant growth activity equivalent to those of thepresent invention. For example, in Chemical Abstracts, Vol. 66, abstract27,927, and Vol. 65, page 5,488, there is disclosed the compound ethylN,N-diethyl-P-chloromethyl phosphonamidate, which is related to thecompounds of the present invention, but the presence of the chloromethylgroup negates its value in the plant growth area as it cannot releasethe ethylene plant growth stimulant and hormone. In addition, in US.Pat. No. 3,010,986, there is disclosed the cyclohexyl ester ofN,N-diallyl-P-(2chloroethyl)-phosphonamidate, prepared by the reactionof 2-chloroetl1yl phosphonyl dichloride and cyclohexanol followed by thereaction of this intermediate with diallyl amine. Also, in ChemicalAbstracts, Vol. 42, page 7,243, the compound 2-chloroethyI-NphenyI-P-(2-chloroethyl) phosphonamidate is suggested as being prepared from itsacid chloride and aniline. In none of these prior art teachings however,is there a disclosure of the 2-chloroethyl-N-substituted phosphoruscompounds of this invention and in particular, 2- chloroethylN-mono-substituted phosphorus compounds which have valuable activity asplant growth stimulants. Accordingly, there is a clear need in the artfor products of this type and processes by which they may be prepared.

SUMMARY OF THE INVENTION It is accordingly one object of this inventionto provide a new class of compounds comprising N-mono-substituted-P( 2-chloroethyl) phosphonamidates.

A further object of the invention is to provide economical processes bywhich these products may be produced.

It is a still further object of the invention to provide N-mono-substituted-P-(2-chloroethyl) phosphonamidate esters which may beprepared from readily available materials in an economic manner as wellas procedures for their use as plant growth regulators.

Other objects and advantages of the present invention will becomeapparent as the description thereof proceeds.

In satisfaction of the foregoing objects and advantages, there areprovided by this invention plant growth regulators of the followingformula:

l Cl-GH CH -NH-R1 wherein R is a halophenyl radical ofthe formula (Hal)1,

wherein Hal is a halogen (e.g. chlorine, bromine, iodine or fluorine,but preferably chlorine), and n is an integer from 1 to 5, preferably 1to 2, the halogen atoms being on any position on the phenyl ring,preferred radicals being 4-chlorophenyl, 3,4-dichlorophenyl,2-chlorophenyl, 3chlorophenyl, 3,4,5- trichlorophenyl and thecorresponding bromo-substituted analogs, and R is alkyl of one to sevencarbon atoms, (e.g. methyl, ethyl, propyl, etc.) or haloalkyl of aboutone to seven carbon atoms, and preferably, haloalkyl wherein thehalogen, which may be chlorine, bromine, iodine or fluorine, butpreferably chlorine, and preferably on the beta-carbon atom, forexample, 2-chloroethyl, 2-chloropropyl, etc.

DESCRIPTION OF PREFERRED EMBODIMENTS It has been found that theabove-identified 2chloroethyl mono-nitrogen-substituted phosphonamidicesters have unique activity as plant growth regulators and may beapplied to plants such as pineapples, soy beans, tomatoes, small grainsand the like to regulate growth and improve crop yields thereof. Thus,these compounds may be stated to be plant growth hormones as theyoperate to increase yields of the products mentioned as well as others.

The compounds of this invention are soluble in varying degrees in waterand so they can be applied to the plants in aqueous solutions composedwholly or partially of water; partial solutions include those formed ofwater and say acetone or methyl ethyl ketone. Any aqueous medium may beused provided that it is not toxic to the plant. Where any particularderivative is less water-soluble, it may be solubilized by the use ofco-solvents and the like. Also, the compounds may be adsorbed on solidcarriers such as vermiculite, attaclay, talc and the like forapplication in granular form. Dusts may also be used in which case theactive ingredient(s) will be diluted with clays or other powders, forexample pyrophyllite, diatomaceous earth and attapulgite.

The compounds can be applied to the plants at a concentration of fromre-l0 lbs/Acre or higher, dependent on the particular derivative used. Apreferred rate of application ranges from 2-5 lbs/Acre. The compoundsneed only be applied to the plant in low volumes of water to achievesatisfactory initiation, and this is an important advantage of thisinvention. Whereas it is necessary to apply the known agents in largevolumes of water, of the order of 200-400 gallons/Acre, even up to 1,000gallons/Acre in the case of ethylene to achieve flower initiation, it ispossible to apply a compound of this invention in far lower volumes ofwater to achieve satisfactory flower initiation. For example, the activecompounds of this invention can be applied in 50 gallons of water at therate of l lb./Acre to achieve percent flower induction on pineapples ofthe Smooth Cayenne variety. The ability to apply the agent in a reducedvolume of water is a great agronomic advantage because a larger acreageof plantation can be treated before recourse to a water supply isnecessary, smaller equipment can be used and costs can be reducedgenerally.

The compounds of this invention may be prepared by the reaction of2-chloroethyl phosphonohalidic esters of the following formula:

wherein R is as above and X is halogen, preferably chlorine, with anamine of the formula:

H N R wherein R is as above, in the presence of a suitable acidacceptor, the acceptor being employed to remove the hydrogen halideformed during the reaction. Preferred amines for use in the reaction are4-chloroaniline and 3,4-dichloroanilinc. The

acid acceptor may be provided by use of an excess of the amine or may beprovided by utilization of any other acid acceptor well known to theart. Preferred acid acceptors are the tertiary amines such astriethylamine, trimethylamine, pyridine, etc. as well as mixturesthereof. Also inorganic acid acceptors may be employed such as alkalimetal hydroxides (e.g. NaOH and KOH), alkali metal carbonates (Na COalkali metal bicarbonates NaHCO and the like.

The reaction is conducted in the presence of a solvent which haspreferably been dried to remove water prior to use. Preferred solventsto be employed in the process include diethyl ether, dioxane, petroleumether, aromatic hydrocarbons (e.g. benzene, toluene), etc., as well asmixtures thereof.

The reaction is conducted at atmospheric pressure and at about roomtemperature (e.g. 20 to 30 C). The reactants are contacted in aboutstoichiometric quantities unless an excess of the amine is employed asthe acid acceptor.

The process is preferably conducted by charging the amine to thesolvent, and the phosphorus-containing compound added thereto at roomtemperature. Generally, either an excess of the amine or another acidacceptor is included in the amine/solvent solution.

After the materials have been mixed, the reaction is generally agitatedfor about 6to 24 hours at room temperature, the amine salt removed byfiltration and the resulting filtrate freed of solvent to provide theproduct of the invention.

The starting materials in this invention may be prepared in any desiredmanner but are preferably prepared by the reaction of phosphoruspentahalide with the diester of 2chloroethyl phosphonic acid of thefollowing formula:

ll CICHaCHz-P (0 R wherein R is as above, which then yields the2-chloroethyl I phosphonohalidate of the following formula:

wherein X is as above. In this reaction it is of course preferable touse a bis ester in which both of the R groups are the same so that onlya single 2-chloroethyl phosphonohalidate is formed rather than a mixturethereof.

This reaction is generally conducted by charging the ester of2-chloroethyl phosphonic acid to a reactor and adding an equivalentamount of the phosphorus pentahalide slowly thereto, preferablyportionwise, while maintaining the temperature below about 80C.Thereafter, after the addition is complete, heating the mixture atreflux for about 2 hours and distilling the resulting product, willprovide the intermediate.

In an alternative procedure, the starting materials may be prepared bythe reaction of an alcohol of the formula ROl-l wherein R is as above,such as absolute ethanol, on 2chloroethyl phosphonyl dihalide at atemperature of about 10 to C. in the presence of an acid acceptor suchas those mentioned above to provide the intermediate after removal ofthe salt and solvent.

. The following examples are provided to illustrate the compounds andprocesses of the present invention.

EXAMPLE I Z-Chloroethyl 2Chloroethylphosphonochloridate: There wascharged 889.5 grams (3.3 moles) of and 686.5 grams (3.3 moles) ofphosphorus pentachloride added portionwise while maintaining thetemperature below C. The mixture was then refluxed for 2 hours at a pottemperature of l07-109C. The volatile materials were removed underaspirator vacuum to a final pot temperature of 120C. The residue wasthen distilled under vacuum. There was ob-' tained 646.8 g. of productboiling at 105l20C. at 1 mm. pressure. This product was redistilledthrough a X 12 inch Vigreaux head. There was obtained 536.0 gramsboiling at 104bLC. at 0.25-0.30 mm. pressure, the product of structurewhich was used as the starting material for Example 3 below.

' EXAMPLE 2 I Ethyl 2-Chloroethylphosphonochloridate:

There was charged to a reaction flask: 100.8 grams (0.55 mol) of2-chloroethylphosphonyl dichloride,

and 500 ml. dry diethyl ether. At a temperature of 0-5C. there was addeda solution of 23.0 grams (0.5 mole) absolute ethanol in 150 ml. dryether followed by a solution of 50.5 grams 0.5 mole) triethylamine inml. dry diethyl ether. The resulting amine hydrochloride was filteredoff and washed with ether. The filtrate was freed from solvent on theflash evaporator and the residue distilled. There was obtained 66.0grams of product boiling at 45-48C. at 0.07 0.09 mm. pressure of thestructure which was used as the starting material for Example 4 below.

EXAMPLE 3 2-Chloroethyl N-( 3 ,4-Dichlorophenyl )-P-( 2-chloroethyl)phosphonamidate:

A solution of 32.4 grams (0.2 mole) of 3,4-dichloroaniline in 500 ml.dry benzene was treated dropwise with 22.5 grams (0.1 mole) of2-chloroethyl 2- chloroethylphosphonochloridate from Example 1. Themixture was left stirring overnight at room temperature. The insolublematerial was filtered off and washed with benzene. The filtrate washeated to boiling on the steam bath, treated with nuchar and againfiltered. The filtrate was evaporated to constant weight. The residuewas triturated in a mortor with 100 ml. 11 0. The solid product wascollected on a filter, washed with water, and dried. Yield 25.2 gramsAnalysis 0 OCzHtCl {l/ 01 Calcd Found 010111 112 H %N 4.01 3.80 \1, 01as? 8.83 9.05

io n a EXAMPLE 4 Ethyl N-(3,4-dichlorophenyl)-P-(2-chloroethyl)-phosphonamidate:

A solution of 32.4 grams (0.2 mole) of 3,4-dichloroaniline in 500 ml.dry benzene was treated dropwise with 19.1 grams (0.] mole) ethyl2-chloroethylphosphonachloridate from Example 2. The mixture was leftstirring overnight at room temperature. The insoluble material wasfiltered ofi and washed with benzene. The filtrate was heated to boilingon the steam bath, treated with nuchar and again filtered. The filtratewas evaporated to constant weight. The residue was triturated in amortar with 100 ml. H O. The solid product was-collected on a filter,washed with water; and dried.

Yield:25.2 grams of a product of the formula OCzH [I O1 ClCHzCHaP HEXAMPLE 5 2-Chloroethyl-N-(4-Bromophenyl)-P-(2-chloroethyl)-Phosphonamidate:

The reaction of Example 3 was repeated except that 0.2 mole of4-bromoaniline was employed in placeof the 4- chloroaniline. From thisreaction, there was recovered 27.6 grams of a compound of the followingformula:

The reaction of Example 4 was repeated except that 0.2 mole of3,4,5-trichloroaniline was used in place of the 3,4- dichloroaniline.From this reaction, there was recovered 28.7 grams of a compound of thefollowing formula:

The reaction has been described herein with reference to certainpreferred embodiments. However, the invention is not to be considered aslimited thereto.

What is claimed is:

l. Substituted Z-chloroethyl' phosphonamidic esters of the followingformula:

( (llaP-lla wherein R is halophenyl of the formula:

wherein Hal is chlorine, bromine, iodine or fluorine and n is an integerfrom 1 to 5, and R is alkyl of one to seven carbon atoms or haloalkyl ofone to seven atoms.

2. compound according to claim 1 wherein R IS 4-

2. A compound according to claim 1 wherein R1 is 4-bromophenyl and R2 is2-chloroethyl.
 3. A compound according to claim 1 wherein R1 is4-chlorphenyl and R2 is ethyl.
 4. A compound according to claim 1wherein R1 is 3,4-dichlorophenyl and R2 is 2-chloroethyl.
 5. A compoundaccording to claim 1 wherein R1 is 3,4,5-trichlorophenyl and R2 isethyl.
 6. A compound according to claim 1 wherein R1 is3,4-dichlorophenyl and R2 is ethyl.